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Methylation is one of the most common and considerable modifications in biological systems mediated by multiple enzymes. Recent studies have shown that methylation has been widely identified in different RNA molecules. RNA methylation modifications have various kinds, such as 5-methylcytosine (m5C). However, for individual methylation sites, their functions still remain to be elucidated. Testing of all methylation sites relies heavily on high-throughput sequencing technology, which is expensive and labor consuming. Thus, computational prediction approaches could serve as a substitute. In this study, multiple machine learning models were used to predict possible RNA m5C sites on the basis of mRNA sequences in human and mouse. Each site was represented by several features derived from k -mers of an RNA subsequence containing such site as center. The powerful max-relevance and min-redundancy (mRMR) feature selection method was employed to analyse these features. The outcome feature list was fed into incremental feature selection method, incorporating four classification algorithms, to build efficient models. Furthermore, the sites related to features used in the models were also investigated. [ABSTRACT FROM AUTHOR]